Our goal is to increase fundamental knowledge of factors that govern nerve fiber growth, formation of appropriate connections in target tissues, and modifications of these connections following experimental manipulation. The individual projects seek to investigate: a) if Schwann cells or fibroblasts from peripheral nerve provide trophic support for neurons (in tissue culture) and if these cells, aligned in "bridges", foster axonal regrowth in damaged spinal cord (in the animal), b) the success of axonal growth and connection formation of normal and modified "substrata" and in the absence of the usual targets in CNS tracts in fetal and neonatal animals, c) the correlation of developing synaptic activity with fine structural changes in growth cone and target cell during synapse formation, d) the signals that govern synthesis of specific proteins that may play a key role in axonal regeneratio, e) the development of a culture system to determine the role of glia in migration of nerve cells derived from normal and genetically abnormal animals, f) the pharmacological basis for plasticity in the visual cortex, g) physiological and anatomical differences between animals lesioned in infancy or adulthood with only the former exhibiting behavioral plasticity, and h) if learning can be detected at the cellular level in the cerebellum and thus serve as a model for studying adaptive control of behavior. The nine investigators involved bring expertise in diverse experimental paradigms and techniques. The purpose of this proposal is to seek funds to support shared facilities (computer, electron micro scopy, and animal support) and to stimulate interaction and collaboration to facilitate progress toward the goal of better understanding basic mechanisms of neuronal growth and interactions. We need new knowledge of mechanisms by which axonal regeneration and useful plasticity occur if we are to successfully intervene to prompt regeneration in the CNS of afflicted human patients.